Summary How cells respond to light and/or timing signal is a fundamental question in biology. Cryptochromes (CRYs) are evolutionarily conserved blue light receptors or the core circadian clock components found in all major evolutionary lineages, from bacteria to human. Our long-term goal is to understand the molecular mechanisms underlying cryptochrome signal transduction and regulation, using Arabidopsis CRY2 as a model system. Arabidopsis CRY2 is presently the best- studied plant cryptochrome. My laboratory has discovered most known aspects of the function and signal transduction mechanisms of CRY2. In the previous funding cycle, we discovered the photoactivation and regulatory mechanisms of CRY2. We found that photoexcited CRY2 undergoes homodimerization to become active; photoactivated CRY2 is inactivated by the Blue- light Inhibitors of Cryptochrome (BIC1 and BIC2). Photoactivated CRY2 is also phosphorylated by four Photoregulatory Protein Kinases (PPK1-4) on at least 24 serine and threonine residues. Phosphorylated CRY2 is not only fully active but also undergoes ubiquitination and degradation. However, several important questions of CRY2 signal transduction remain unsolved, including how CRY2 mediate light regulation of transcriptional and post-transcriptional changes of gene expression to modulate plant development and how CRY2 itself is regulated by light to modulate photosensitivity of plants. This renewal application attempt to address those questions based on results of our recent experiments.